Antibodies in Mom Linked to Autism in Kids

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Researchers identified seven primary fetal brain antigens which are recognized by maternal autoantibodies in almost one-quarter of mothers of ASD children.

In a second study, IgG isolated from mothers of children with ASD was administered to pregnant rhesus monkeys and was associated with inappropriate social interactions in the offspring.

Maternal autoantibodies that target key proteins in the fetal brain could explain almost one in four cases of autism, according to two studies published online this week in the journal Translational Psychiatry.

In one study, researchers from the University of California, Davis MIND Institute identified seven antigens specific to autism and then showed that the antibodies to these antigens were present in the blood of 23% of mothers who had children with the disorder and less than 1% of mothers with normally developing children.

In a second study, female rhesus monkeys exposed while pregnant to the autism-specific antibodies from the blood of mothers of children with autism gave birth to offspring that displayed behavioral traits consistent with the disorder. Male monkeys, but not females, born to the antibody-exposed mothers also had brain growth patterns consistent with male children with autism, seen in neuroimaging studies.

The identification of the autism-specific maternal autoantibodies could lead to a maternal blood test to help identify children at risk for autism spectrum disorder long before symptoms manifest, said researcher Judy Van de Water, PhD, who worked on both studies.

Van de Water and UC Davis colleague Daniel Braunschweig, PhD, have patented the autism-specific proteins and the San Diego-based company Pediatric Bioscience is currently working to develop just such a test. Van de Water is a consultant for the company and she is a member of its scientific advisory board.

She told MedPage Today that the maternal blood test could be commercially available in as little as a year and a half.

"The first market would probably be high-risk moms who may already have a child with autism, or those with very young children suspected of having developmental delays," she said. "The earlier we can identify autism and related disorders, the earlier interventions can begin."

About one in 88 children in the U.S. are estimated to have an autism spectrum disorder, according to the latest figures from the CDC.

In earlier studies, Van de Water and colleagues found that women with certain antibodies had a greater risk of having children with autism and that these children exhibited more severe symptoms than other children on the spectrum.

In the newly published study, the researchers examined blood samples from 246 mothers of children with autism and 149 mothers of normally developing children in an effort to identify specific antigens associated with autism.

They found seven antigens that were significantly more reactive to the blood of mothers with autistic children than control mothers.

The antigens included:

Lactate dehydrogenase A and B

Cypin (guanine deaminase)

Stress-inducing phosphoprotein 1 (STIP1)

Collapsing response mediator proteins 1 and 2 (CRMP1, CRMP2)

Y-box binding protein

The proteins are found throughout the body, but are expressed at high levels in the fetal brain and they all are involved in neurodevelopment.

Mothers with antibodies that reacted with any one of the antigens, either individually or in combination, were more than three times as likely to have a child on the autism spectrum.

In the rhesus monkey study -- led by UC Davis researcher Melissa Bauman, PhD -- antibodies from human mothers with and without children with autism were injected into pregnant monkeys.

Offspring born to mothers injected with the autism-specific antibodies displayed abnormal social behaviors not seen in the controls. These behaviors included inappropriate approaches to unfamiliar peers, which is unusual for young rhesus monkeys. The mothers of these monkey were also more protective of their offspring even before these abnormal social behaviors were exhibited.

"The protective maternal style was observed only when other animals were present, suggesting that the mothers perceived a greater risk to their infants in the context of the group interaction," the researchers wrote. "It is plausible that the mothers detected subtle behavioral abnormalities in (these) offspring that eluded our observations..."

Van de Water said larger studies are needed to better understand the role of the identified proteins in autism. She added that studies are currently underway to assess the predictive value of the autoantibodies in a prospective study sample.

The researchers conclude that the clinical significance of the findings may include not only earlier diagnosis of a subset of children with autism spectrum disorder, but medical interventions that may prevent autism by blocking exposure to these antibodies in children born to affected mothers.

Autism specialist Andrew Adesman, MD, called the research intriguing and said the studies warrant further investigation. But he agreed that larger studies will be needed before the clinical significance of the autism-specific autoantibodies are understood.

"Based on what the researchers are reporting so far this may be a helpful test for identifying children at risk for autism, but they have a long way to go before they can even think about using this for screening," he told MedPage Today. "There are just too many unanswered questions."

The Braunschweig et al. study was funded by grants from the U.S. Environmental Protection Agency, the NIEHS, the UC David M.I.N.D. Institute and Autism Speaks.

The Bauman et al. study was funded by grants from the National Institute of Mental Health, the California National Primate Research Center and the UC Davis M.I.N.D. Institute.

Braunschweig and Van de Water have a published patent on the proteins described in the study. Van de Water is also a consultant for the company Pediatric Biosciences, which has licensed the technology from UC Davis.

Researchers J. Van de Water and D.G. Amaral, who was corresponding author for the Bauman et al. study, are members of the scientific advisory board for Pediatric Biosciences. The researchers report that Pediatric Biosciences did not contribute in any way to the current studies.

The remaining authors for both studies declared no conflict of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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